Table 1.
Summary of human studies investigating the association between pancreatic steatosis and glucometabolic disorders
| First author (reference) | Study design and population | Assessment of pancreatic steatosis | No. patients | Prevalence of fatty pancreas | Assessment of β‐cell function | Results |
|---|---|---|---|---|---|---|
| Tushuizen et al. (2007)43 | Case‐control study; Caucasian men; aged 35–65 years; alcohol intake <20 units/week | 1H‐MRS |
Total: 36 Subgroup: 12/24 (type 2 diabetes/non‐type 2 diabetes) |
– | OGTT‐derived insulinogenic index |
Patients with type 2 diabetes have higher pancreatic fat content than those with non‐type 2 diabetes. Pancreatic fat content negatively correlates with β‐cell function only in non‐type 2 diabetes group. Pancreatic fat content is not associated with BMI, WC, TG, FFAs, VAT, hepatic fat content |
| Al‐Haddad et al. (2009)53 | Case–control study in USA; patients who underwent EUS; median age 65 years | EUS |
Total: 120 Subgroup: 60/60 (hyperechogenic pancreas/healthy control) |
– | – | Hyperechogenic pancreas is associated with BMI, hepatic steatosis, alcohol use |
| Lee et al. (2009)15 | Cross‐sectional study in South Korea; adults visiting an obesity clinic; mean age 44.9 ± 9.5 years; alcohol intake <20 g/day in women and <40 g/day in men | Abdominal US |
Total: 293 Subgroup: 180/113 (NAFPD/non‐NAFPD) |
61.4% | – |
HOMA‐IR, TG and VAT tend to increase with the degree of NAFPD. The incidence of metabolic syndrome and the number of metabolic syndrome parameters are higher in NAFPD group compared with in the control group |
| Lingvay et al. (2009)30 | Cross‐sectional study in USA; volunteer with normal or abnormal glucose tolerance; alcohol intake <2 units/day | MRS |
Total: 79 Subgroup: 15/30/23/11 (NGT plus BMI <25/NGT plus BMI ≥25/IGT or IFG/type 2 diabetes) |
– | – |
In normoglycemic population, overweight or obese subjects have higher pancreatic fat content compared with lean subjects. Subjects with similar BMI, but with abnormal glucose tolerance (IGT or IFG, or type 2 diabetes) have even higher pancreatic fat content. Post‐challenge blood glucose level has the strongest relationship to pancreatic fat content. Pancreatic and hepatic fat contents are only weakly correlated |
| van Greenen et al. (2010)14 | Retrospective study in the Netherlands; deceased adults who underwent autopsy; mean age of death 68 ± 14 years; alcohol intake <14 units/week in women and <21 units/week in men | Pathology | Total: 80 | – | – |
Intralobular pancreatic fat is associated with non‐alcoholic steatohepatitis. Total pancreatic fat is a significant predictor for NAFLD |
| Choi, et al. (2010)18 | Cross‐sectional study in South Korea; subjects who underwent EUS; mean age 52.1 ± 12.2 years | EUS |
Total: 284 Subgroup: 110/174 (hyperechogenic pancreas/non‐ hyperechogenic pancreas) |
38.7% | – | Hyperechogenic pancreas is associated with fatty liver, male, aged >60 years, hypertension, and VAT |
| Heni et al. (2010)19 | Cross‐sectional study in Germany; healthy Caucasian subjects with increased risk of type 2 diabetes | MRI |
Total: 51 Subgroup: 23/28 (IFG and/or IGT/NGT) |
– | OGTT‐derived insulinogenic index |
Pancreatic fat content negatively correlates with insulin secretion only in subjects with IGT and/or IFG. Pancreatic fat content positively correlates with BMI, VAT, and WC. No association of pancreatic fat contents with age, sex and hepatic fat content |
| Rossi et al. (2011)20 | Cross‐sectional study in Italy; obese subjects without diabetes; mean age 49.1 ± 13.0 years; alcohol intake <20 g/day in women and <30 g/day in men | MRI |
Total: 38 Subgroup: 18/20 (men/women) |
– | – |
Obese subjects had higher pancreatic fat content than lean subjects. Obese men had higher pancratic fat content than obese women despite same BMI. Pancreatic fat content is positively related with WC, VAT, TG and fat intake, and negatively related to adiponectin. No association between pancreatic fat content and insulin resistance |
| Lê et al. (2011)44 | Cross‐sectional study; young obese African Americans or Hispanics; aged 13–25 years | MRI |
Total: 138 Subgroup: 74/64 (Hispanic/African American) |
– | IVGTT‐derived disposition index |
Hispanics had higher pancreatic fat content than African Americans, and the ethnic difference becomes greater with increasing age. Pancreatic fat content is positively associated with VAT, hepatic fat content and FFAs. No association between pancreatic fat content and insulin sensitivity or β‐cell function |
| Sepe et al. (2011)26 | Cross‐sectional study in USA; patients who are referred for EUS; mean age 62.9 ± 13.9 years | EUS |
Total: 230 Subgroup: 64/166 (fatty pancreas/non‐fatty pancreas) |
27.8% | – |
The presence of fatty pancreas is associated with BMI, fatty liver, hyperlipidemia and metabolic syndrome. Subjects with increasing number of metabolic syndrome parameters have a higher risk of fatty pancreas. No association between fatty pancreas and chronic pancreatitis or pancreatic adenocarcinoma |
| van der Zijl et al. (2011)45 | Case–control study; overweight Caucasian subjects with a family history of type 2 diabetes; alcohol intake <20 units/week | 1H‐MRS |
Total: 64 Subgroup: 16/29/19 (NGT/IFG/IFG and/or IGT) |
– | Hyperglycemic hyperinsulinemic clamp‐derived disposition index |
Pancreatic fat content gradually increases between NGT, IFG and IFG/IGT. Pancreatic fat content is positively associated with age, BMI and 2‐h plasma glucose, and negatively related to insulin sensitivty and e‐cholesterol. No association between pancreatic fat and β‐cell function |
| Ou et al. (2013)23 | Cross‐sectional study in Taiwan; adults who underwent health check‐up; alcohol intake <20 g/day | Abdominal US |
Total: 7,464 Subgroup: 5,756/1,225/483 (NGT/prediabetes/diabetes) |
– | – |
The prevalence of NAFPD gradually increases between NGT, prediabets and diabetes. NAFPD is associated with an increased risk for diabetes. NAFPD is related to prediabetes only in men, but not in women |
| Wu et al. (2013)24 | Cross‐sectional study in Taiwan; adults who underwent health check‐up; mean age 50.8 ± 12.4 years | Abdominal US |
Total: 557 Subgroup: 72/485 (fatty pancreas/non‐fatty pancreas) |
12.9% | – |
Subjects with fatty pancreas have a greater proportion of obesity, hypertension, dyslipidemia (e.g., high TG, low HDL‐cholesterol) and hyperglycemia than those without fatty pancreas. The incidence of metabolic syndrome and the numbers of metabolic syndrome parameters are higher in subjects with fatty pancreas compared with in the control group |
| Wong et al. (2014)32 | Cross‐sectional study in Hong Kong; healthy adults; mean age 48 ± 10 years; alcohol intake <10 g/day (<70 g/week) in women and <20 g/day (<140 g/week) in men | MRI |
Total: 685 Subgroup: 110/575 (NAFPD/non‐NAFPD) |
16.1% | HOMA‐β |
NAFPD is more common in men and in postmenopausal women. Subjects with both NAFPD and NAFLD had higher HOMA‐IR than did those with either condition alone NAFPD is associated with central obesity, hypertriglyceridemia, hyperferritinemia and insulin resistance. No association between NAFPD and β‐cell function |
| Wang et al. (2014)16 | Cross‐sectional study in Taiwan; adults who underwent health check‐up; alcohol intake <20 g/day | Abdominal US |
Total: 8,097 Subgroup: 1,297/6,800 (NAFPD/non‐NAFPD) |
16.0% | – |
Subjects with NAFPD have a greater proportion of diabetes and NAFLD than those without NAFPD. NAFPD is associated with age, obesity, diabetes and NAFLD |
| Lesmana et al. (2015)25 | Cross‐sectional study in Indonesia; adults who underwent routine medical check‐up; mean age 43.1 ± 12.19 years; alcohol intake <20 g/day | Abdominal US |
Total: 901 Subgroup: 315/586 (NAFPD/non‐NAFPD) |
35% | – | NAFPD is associated with age >35 years, male sex, obesity, hyperglycemia, higher blood pressure, dyslipidemia and NAFLD |
| Della Corte et al. (2015)17 | Cross‐sectional study in Italy; consecutive children and adolescents with NAFLD; mean age 13.16 ± 2.69 years | Abdominal US |
Total: 121 Subgroup: 58/63 (NAFPD/non‐NAFPD) |
48% | – |
Subjects with NAFPD have a higher BMI, inflammatory cytokine (e.g., TNF‐a, IL‐1β), fasting insulin, insulin resistance, and lower insulin sensitivity index compared with those without NAFPD. NAFPD is positively associated with hepatic fibrosis, steatosis and NAFLD activity score. No association between NAFPD and IL‐6 |
| Begovatz et al. (2015)29 | Cross‐sectional study in Germany; Caucasian subjects; alcohol intake <10 g/day in women and <20 g/day in men | MRI and 1H‐MRS |
Total: 56 Subgroup: 28/14/14 (NGT/IFG and/or IGT/type 2 diabetes) |
– | OGTT‐derived insulinogenic index |
Pancreatic fat consists of an inhomogenous distribution of adipose tissue infiltration instead of uniform pancreatic steatosis. Pancreatic fat infiltration increased with age and decreasing glucose tolerance. No association of pancreatic fat infiltration with β‐cell function regardless of glucose tolerance status |
| Yamazaki, et al. (2016)28 | 5‐year retrospective cohort study in Japan; volunteer who underwent a health check; mean age 51.8 ± 9.8 years | CT scan |
Total: 813 New‐onset type 2 diabetes during follow‐up: 62 (7.6%) |
– | – |
Pancreatic steatosis at baseline is positively associated with incident type 2 diabetes in a univariate analysis; however, the association disappears after adjustment for potential confounders (i.e., age, sex, BMI, liver attenuation and alcohol intake). Pancreatic steatosis is not independently associated with future type 2 diabetes |
BMI, body mass index; CT, computed tomography; EUS, endoscopic ultrasonography; FFA, free fatty acid; HDL‐C, high‐density lipoprotein cholesterol; HOMA‐β, the homeostasis model assessment of β‐cell function; HOMA‐IR, the homeostasis model assessment of insulin resistance; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; IL‐1β, interleukin‐1β; IL‐6, interleukin‐6; IVGTT, intravenous glucose tolerance test; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; NAFLD, non‐alcoholic fatty liver disease; NAFPD, non‐alcoholic fatty pancreas disease; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; TG, triglycerides; TNF‐α, tumor necrosis factor‐α; US, ultrasonography; VAT, visceral adipose tissue; WC, waist circumference.